Tam E, et al. - In this work, data was reported from two similarly designed studies that evaluated the efficacy, safety, and optimal duration of ledipasvir/sofosbuvir (LDV/SOF) ± ribavirin (RBV) for retreatment of chronic hepatitis C virus (HCV) in individuals who failed to achieve sustained virologic response (SVR) with prior SOF-based, non-NS5A inhibitor-containing regimens. Researchers observed high SVR at 12 weeks in SOF-experienced NS5A inhibitor-naïve population, that included participants with cirrhosis or HCV/HIV co-infection.

Methods

• HCV mono-infected adults with genotype 1 or 4 were enrolled in the RESCUE study.
• Randomization of non-cirrhotic participants was performed to 12 weeks of LDV/SOF or LDV/SOF+RBV.
• Researchers randomized compensated cirrhotic participants to LDV/SOF+RBV (12 weeks) or LDV/SOF (24 weeks).
• Genotype 1 adults with HCV/HIV co-infection in the AIDS Clinical Trials Group A5348 study were randomized to LDV/SOF+RBV (12 weeks) or LDV/SOF (24 weeks).
• SVR at 12 weeks post-treatment (SVR12) was assessed as the primary endpoint by both studies.

Results

• Eighty two participants were randomized and treated in the RESCUE study; all completed treatment.
• Overall, SVR12 of 88% (72/82) was observed; 81-100% in non-cirrhotic participants treated with LDV/SOF or LDV/SOF+RBV for 12 weeks and 80-92% in cirrhotic participants treated with LDV/SOF+RBV for 12 weeks or LDV/SOF for 24 weeks.
• Mostly mild-to-moderate adverse events (AEs) were experienced by 78% of participants; headache and fatigue were most frequently reported.
• Researchers noticed one serious AE, not related to treatment.
• They observed no premature discontinuations of study drug, or deaths.
• Seven participants were randomized (cirrhotic n=1; GT1a n=5) in the A5348 study; all attained SVR12, with no serious AEs or premature discontinuations.